Composite Coatings of Oxidized and/or Phosphorous Copper

Abstract

The present invention relates to a synthetic coating containing oxidized and/or phosphorous copper, the method for obtaining the coating and the uses of said coating. The present invention further relates to an oxidized and/or phosphorous copper powder making it possible to obtain the coating of interest, the method for manufacturing said coating and its uses.

Claims

1-17. (canceled)

18. A composite characterized in that it comprises a powder composition of oxidized and/or phosphorized copper powder wherein said powder: contains at least 60% by mass of copper, contains not more than 70% by mass of grains the diameter of which is less than 45 m at most, and a binding agent.

19. The composite according to claim 18, characterized in that the phosphorized copper powder is in the form of CuP.sub.8.

20. The composite according to claim 18, characterized in that the composite further comprises a curing catalyst.

21. The composite according to claim 18, characterized in that the copper is oxidized to the core.

22. The composite according to claim 18, characterized in that the oxidation ratio of the copper is greater than 95% by mass of oxidized copper relative to the total mass of copper and/or in that the amount of phosphorus is between 2% and 16% by mass relative to the total mass of powder.

23. The composite according to claim 22, characterized in that the amount of phosphorus is 8% by mass relative to the total mass of powder.

24. The composite according to claim 18, characterized in that said composite comprises: at least one metal other than copper, and/or at least one nonmetallic inorganic compound.

25. The composite according to claim 24, characterized in that the metal is selected from the group consisting of magnesium, tin, technetium, rhenium, iron, chromium, cobalt, zinc, platinum, cadmium, aluminum, nickel, silver, beryllium, calcium, and strontium.

26. The composite according to claim 25, characterized in that the metal is magnesium.

27. The composite according to claim 24, characterized in that the nonmetallic inorganic compound is selected from the group consisting of nitrogen, arsenic, sulfur, fluorine, chlorine, bromine, carbon and silicon.

28. The composite according to claim 18, characterized in that the binding agent is an organic polymer selected from the group consisting of polyester, polyurethane, an epoxy, and vinyl ester polymer.

29. The composite according to claim 18, characterized in that the binding agent is an inorganic polymer selected from the group consisting of silica, polydimethylsiloxanes, polythiazyls, polysilanes, and polygermanes.

30. The composite according to claim 29, characterized in that the inorganic polymer is a silica polymer.

31. The composite according to claim 30, characterized in that the silica polymer is a glass.

32. The composite according to claim 18, characterized in that the proportion by mass of powder to binder in the composite is from 1/2 to 2/1, respectively.

33. The composite according to claim 32, characterized in that the proportion by mass of powder to binder in the composite is 1.275/1, respectively.

34. A method for preventing nosocomial diseases comprising the use of the composite according to claim 18 as a biocide.

Description

FIGURES

[0291] FIG. 1: Change in the logarithm of the total number of CFU over time

EXAMPLES

[0292] In order to illustrate the present invention, the following examples were carried out. In no case is the object of the present invention limited to these examples alone. [0293] 1. CuP.sub.8-based Powder

[0294] CuP.sub.8 powder, the particle size of which is not controlled, is known to be used in brazing.

[0295] Traditionally, it has the following features: [0296] Nominal composition (mass %): Cu: 92 [0297] P: 8 [0298] Point melting: 710-750 C [0299] Density: 8 g/cm.sup.3 [0300] Protocol for Manufacturing the Copper-phosphorus Powder according to the Invention

[0301] According to the present invention, the copper-phosphorus alloy containing a percentage of phosphorus between 2% and 16%, preferably 8%, is introduced into the melt bath. This alloy is then atomized with water under conditions such that the particle size results must be between 8 and 150 m (D50); the oxygen content is between 0.3% and 5% by weight. [0302] The following powder was thus obtained:

TABLE-US-00001 TABLE 1 Particle size, cumulative % retained (ISO 4497) Percentages Cumulative percentages Particle size by interval retained 125 m 0.0 0.0 106 m 0.9 0.9 90 m 4.5 5.4 75 m 6.6 12.0 63 m 8.4 20.4 45 m 20.8 41.2 <45 m 58.8 58.8 Total 100% 100% (41.2 + 58.8) [0303] Density obtained: 2.67 g/cm.sup.3 (ISO 3923/2) [0304] P% obtained: 8.0% by mass [0305] 2. Oxidized Copper Powder [0306] The same protocol as for copper-phosphate was applied for copper.

[0307] The following powder was thus obtained:

TABLE-US-00002 TABLE 2 Particle size, cumulative % retained (ISO 4497) Percentages Cumulative percentages Particle size by interval retained 125 m 0.0 0.0 106 m 1.0 1.0 75 m 8.1 9.1 63 m 7.9 17.0 45 m 19.2 36.2 <45 m 63.8 63.8 Total 100% 100% (36.2 + 63.8) [0308] Density obtained: 2.88 g/cm.sup.3 [0309] O.sub.T%: 0.35% by mass (ISO 4491-4) [0310] Next, the powder obtained passed into a conveyor oven at a temperature above 500 C (about 800 C in the present case) in order to oxidize it, under controlled atmosphere. [0311] A powder with same particle size as before was obtained with: [0312] density: 1.60 g/cm.sup.3 [0313] O.sub.T%: 0.08% by mass [0314] Cu%>99.7% by mass [0315] 3. Example of the Composite/Coatings Obtained

[0316] The composites are simply obtained by mixing the compounds together.

[0317] The coatings in Table 3 were applied in the following traditional manner.

[0318] First, the surface to be treated is sanded (120 grain). In the case of a metal surface, it is possible to apply an insulating anti-corrosion primer suited to the nature of the substrate (ferrous, nonferrous, etc.). In the case of a porous surface (stone, wood, etc.), it is possible to apply a polyester primer in two coats, if need be with roughing (120 grain) between coats.

[0319] It is strongly advised to respect the curing times of the polyester primer (about 6 hours at 20 C per coat) so that the thin layer endures over time. Next, the part can undergo active drying with compressed air or by baking at 25 C in an enclosure for 20 minutes. It is possible to degrease the surface to be treated.

[0320] It is quite possible to apply the composite by means of a roller or gun (with, in this case, the need to project the composite onto the surface at a constant angle of 90 for maximum coverage).

[0321] The coated product can be stored in a room with a controlled atmosphere at 20 C, ideally for 12 hours for effective curing (for a boat this is more difficult to obtain, which is why curing accelerators are used to carry out catalysis at up to 5 C minimum). Once this curing period is over, sanding (120 grain) is carried out in order to strip the surface of excess starch and oxides and to obtain a smooth metal surface.

TABLE-US-00003 TABLE 3 Composite 1 Composite 2 Composite 3 Metal powder CuP.sub.8 (powder of Oxidized copper Oxidized copper Example 1) (powder of (powder of Example 2) Example 2) Binder Hybrid polyester 84% Hybrid polyester 84% Vinyl ester, ready-to- (proportions Acetone 8% Acetone 8% use, available by mass) Styrene wax 2% Styrene wax 2% commercially Colorant 4% Colorant 4% Curing agent METHYL ETHYL METHYL ETHYL (proportions PEROXIDE, 2% PEROXIDE, 2% by mass) Proportions Powder = 1.275 Powder = 1.275 Powder = 1 by mass of Binder = 1 Binder = 1 Binder = 1.5 powder to (estimated binder value) Suspension yes yes yes possible Coating By spraying By spraying By spraying obtained (possible with a (possible with a (possible with a roller) roller) roller) Curing time 60 minutes 60 minutes 60 minutes Approximate 100-250 m 100-250 m 100-250 m thickness of (estimated value) (estimated value) (estimated value) the coating obtained [0322] 4. Examples of Biocidal Activity

[0323] Results of laboratory tests showed that the coatings had remarkable biocidal properties:

TABLE-US-00004 TABLE 4 Mean CFU count on MetalSkin medical versus control; Analysis of raw values (Except treatment/sampling surface) Mean CFU Mean CFU % MetalSkin count/Control count/MetalSkin count/Control Mann-Whitney elements elements count Wilcoxon test test (amplitude) (amplitude) (amplitude) (p value) (p value) Door handle 6 (0-17) 0 (0-10) 0% (0-233) 0.02524 0.00964 (corridor) Door handle 6 (0-18) 0 (0-9) 0% (0-300) 0.00014 0.00002 (ward) Switch, ward 8 (0-16) 0 (0-10) 0% (0-350) 0.00008 0.00002 entrance Shower grab- 13 (0-44) 8 (0-25) 61% (3-300) 0.00291 0.00449 bar Toilet lid 7 (0-31) 0 (0-12) 0% (0-1200) 0.19863 0.23713 Faucet handle 9 (0-20) 6 (0-18) 73% (0-480) 0.00646 0.02163 Adjustable tray 10 (0-21) 0 (0-10) 0% (0-450) 0.00046 0.00009

[0324] Thus, the coatings obtained according to the present invention demonstrate their biocidal (including antimicrobial) properties in various applications, whether in a dry state or in the presence of fluids such as water. [0325] 5. Study of a Copper-containing Composite in Reducing Bacterial Carriage of Elements of an Orthopedic Surgery Ward in a Clinic

[0326] 5.1. Introduction

[0327] In France, nosocomial infections are a significant source of morbidity and mortality. Nearly 4200 deaths per year are attributable thereto. The extra expenditures generated by these infections are evaluated between 2.4 and 6 billion euros per year, notably due to longer periods of hospitalization, antibiotic treatment, laboratory tests and infection monitoring.

[0328] It is known that about 30% of nosocomial infections could be prevented by suitable hygiene measures, including handwashing. The role of the environment in the infectious process seems proven, at least for certain bacteria. The studies carried out have been most interested in objects frequently touched by the hands, which thus become elements of the spread of infection.

[0329] Typical cleanliness measures seem insufficient to ensure this hygiene, even more so as some bacteria remain present for a long time, even after cleaning (in particular in the case of Staphylococcus aureus).

[0330] Measures proposed for decreasing bacterial carriage include the use of active products such as hydrogen peroxide, but also the use of antimicrobial materials for the most frequently used surfaces (door handles, toilet lids, taps, switches, etc.). The application on these surfaces of an antimicrobial material can help to reduce these cross-contaminations. One recognized bactericidal product is copper, which, in vitro, kills many microorganisms, including Escherichia coli, methicillin-resistant Staphylococcus aureus, Listeria monocytogenes, influenza A virus and C. difficile. Copper-based products seem to show advantageous results in vitro and studies by Sasahara and Casey demonstrate a significant decrease in bacteria on surfaces treated with copper.

[0331] However, the cost of solid copper and the large number of locations or objects to be treated make their generalized use relatively improbable or too costly.

[0332] A copper-containing composite according to the present invention was developed for coating handles, taps and another equipment at a lower cost given the small thickness (200 microns) of copper.

[0333] The goal of this study is to show the efficacy of this novel product in terms of antibacterial activity within orthopedic surgery wards.

[0334] 5.2. Methods

[0335] 5.2.1 Clinical Protocol

[0336] The alloy of the product used is copper-phosphorized, with 95% copper. This product was used to coat the objects most frequently used and touched by the hands in wards.

[0337] The experiment concerned six rooms of the orthopedic surgery department of the Saint Roch clinic in Montpellier (France). Among these six rooms, three selected randomly were equipped with the copper-containing product. There are seven elements concerned in each treated room: two door handles (exterior, interior), a switch, an adjustable tray, a toilet lid, a shower grip-bar and a shower knob. The other three rooms kept the usual equipment and thus comprised the control group.

[0338] The study lasted eight weeks. Samples were taken every Monday, Wednesday, Thursday and Friday in each of the six rooms and on each of the seven elements under study. The total number of samples taken is thus 1344.

[0339] For weeks 5 to 8, two rooms were switched around: a treated room became a control and a control room became treated. The diagram of the experimental design is thus as follows:

TABLE-US-00005 TABLE 5 Diagram of the experimental design Room Room Room Room Room Room 1 2 3 4 5 6 Weeks Control Control Control Treated Treated Treated 1-4 Weeks Control Treated Control Control Treated Treated 5-8

[0340] 5.2.2. Microbiological Methodology and Sampling

[0341] The sample is taken on a swab soaked in sterile solution and using a sterile template. Rubbing is carried out 15 times in each direction. Then the swabs are submerged in neutralizing solution, centrifuged and incubated at 37 C for 48 hours. The sampling template is sterile.

[0342] Counting and identification are carried out next.

[0343] Bacterial count: a single laboratory [. . . ] performed the bacterial count.

[0344] The bacterial count was carried out taking into account a positivity threshold. Below 5 CFU per 25 cm.sup.2 of surface area, the count is considered zero.

[0345] In order to standardize the surface areas of the calculation, the latter was set to 100 cm.sup.2 for all the sampling locations. Thus, the calculations for the door handles and the grab-bar were multiplied by 8 and the other locations multiplied by 4. Indeed, for the toilet lid, the adjustable tray, the switch and the taps the surface area is 25 cm.sup.2 while for the door handles and the grab bar it is 12.5 cm.sup.2.

[0346] The rooms are cleaned once per day. Cleaning usually takes place between 9 a.m. and 10 a.m. As for the samples, they were all taken after 4 p.m. (generally between 4 p.m. and 5 p.m.). The exact room cleaning schedule was recorded, as was the sampling schedule. As a result, the period of time between cleaning and sampling could be calculated.

[0347] 5.2.3. Statistical Methods

[0348] 5.2.3.1. Calculation of the Number of Samples Needed

[0349] This calculation was made for each element since the goal is to compare the mean total number of bacteria (bioMrieux identification system) on each sampling site between the control room group and the treated room group. To calculate the number of samples needed, we made the assumption that our results would be close to those obtained in the Birmingham study.

[0350] In terms of overall mean CFU between the treated rooms and the control rooms in the Birmingham study, for the tops of the toilet lids, one passes from 2190 CFU to 6 on mean, with great variability (in the Birmingham study there were only 200 samples). But these toilet lids were very contaminated.

[0351] We thus plan to find a mean of 6 to 15 elements on each site with the controls and from 1 to 8 with the prepared elements. I.e., a minimum mean deviation between 9 and 7, with a standard deviation varying between 2 and 5.

[0352] Looking at the mean case (standard deviation=4) leads to:

[0353] 84 samples on each site (handle, etc.) and per group of rooms (mean deviation=2) and with 10% of the data uninterpretable from 94 samples per group of rooms.

[0354] However, per sampling site, we planned 48 samplings the first 4 weeks (per group of rooms) and 48 the following 4 weeks, for a total of 96. Thus the number planned should be enough to answer the question asked, on all the sites.

[0355] 5.2.3.2. Statistical Analyses

[0356] The total number of CFU, all sampling sites taken together, were first compared between the two groups of rooms. Then, the same comparisons were made by sampling site (seven sites).

[0357] A comparison of the number of colonies of Staphylococcus aureus (MicrococcusBacillus) between the treated rooms and the control rooms was then carried out, with all the sampling sites first considered together and then considered site by site.

[0358] The period of time between cleaning and sampling was also compared between the groups of rooms.

[0359] The nonparametric Wilcoxon-Mann-Whitney test (Mann-Whitney U test) was used for all the comparisons.

[0360] Weeks 1 to 4 and 5 to 8 were differentiated throughout the analysis (because two rooms switched). For the paired case (over 8 weeks), the results are not presented, the lack of power being too great (only 4 rooms remaining).

[0361] Finally, the temporal change in the logarithm of the total number of microorganisms was studied using a mixed model with repeated measures. Indeed, a logarithmic transformation was carried out due to the non-verification of the assumption of normality, needed to carry out the mixed model.

[0362] The statistical analyses were all carried out with SAS software 9.3, SAS Institute Inc., Cary, N.C., USA, by the Biostatistics and Epidemiology team EA 2415 of Montpellier University I.

[0363] 5.3. Results

[0364] 5.3.1. Weeks 1 to 4

[0365] The time between cleaning and sampling was first compared in the two groups of rooms, in order to eliminate this confounding variable. This period does not appear to be statistically different between the groups of rooms, either week by week or over the totality of the first 4 weeks (Table 6). The median period of time varies between 4 and 6 hours.

TABLE-US-00006 TABLE 6 Time between cleaning and sampling - Weeks 1 to 4 All rooms Treatment Control (N = 6) (N = 3) (N = 3) p-value Time between cleaning and sampling Week 1 Mean (SD) 5.28 (1.04) 5.73 (0.74) 4.84 (1.25) 0.6625 Median (Min; Max) 5.48 (3.86; 6.25) 6.08 (4.88; 6.22) 4.42 (3.86; 6.25) Time between cleaning and sampling Week 2 Mean (SD) 4.28 (0.58) 4.45 (0.86) 4.1 (0.17) 1.0000 Median (Min; Max) 4.04 (3.9; 5.44) 4.02 (3.9; 5.44) 4.07 (3.96; 4.29) Time between cleaning and sampling Week 3 Mean (SD) 4.91 (0.92) 5.35 (0.5) 4.47 (1.14) 0.3827 Median (Min; Max) 5.11 (3.19; 5.79) 5.46 (4.81; 5.79) 4.86 (3.19; 5.35) Time between cleaning and sampling Week 4 Mean (SD) 4.79 (0.63) 4.91 (0.45) 4.68 (0.86) 1.0000 Median (Min; Max) 4.96 (3.71; 5.36) 4.96 (4.44; 5.33) 4.96 (3.71; 5.36) Time between cleaning and sampling Weeks 1-4 Mean (SD) 4.82 (0.52) 5.11 (0.56) 4.52 (0.34) 0.3827 Median (Min; Max) 4.72 (4.13; 5.6) 5.22 (4.51; 5.6) 4.72 (4.13; 4.72)

[0366] Table 7 presents the results in the three treated rooms and the three untreated rooms for weeks 1 to 4 cumulatively. Overall, a trend toward significance (nonparametric test) is noted (p=0.0809) with a mean of 685 bacterial colonies (median=685) in the treated group and 1091 (median=1058) in the untreated group. This trend is due to that noted during the second week; however, for the other weeks, a reduction of almost 50% of the median number of microorganism colonies is found, as well as a reduction of more than 1/3 of the mean value.

TABLE-US-00007 TABLE 7 Total number of CFU - Weeks 1 to 4 All rooms Treatment Control (N = 6) (N = 3) (N = 3) p-value Total CFU Week 1 Mean (SD) 247.33 (89.32) 195.67 (85) 299 (68.64) 0.3827 Median (Min; Max) 259.5 (111; 378) 195 (111; 281) 265 (254; 378) Total CFU Week 2 Mean (SD) 224.5 (104.36) 145.33 (46) 303.67 (79.43) 0.0809 Median (Min; Max) 202 (99; 361) 146 (99; 191) 337 (213; 361) Total CFU Week 3 Mean (SD) 202.5 (69.14) 160.67 (79.73) 244.33 (18.56) 0.3827 Median (Min; Max) 235.5 (105; 262) 125 (105; 252) 246 (225; 262) Total CFU Week 4 Mean (SD) 214 (72.47) 183.33 (70.12) 244.67 (73.42) 0.3827 Median (Min; Max) 203.5 (131; 327) 156 (131; 263) 221 (186; 327) Total CFU Weeks 1-4 Mean (SD) 888.33 (228.49) 685 (23) 1091.67 (77.22) 0.0809 Median (Min; Max) 872.5 (662; 1180) 685 (662; 708) 1058 (1037; 1180)

[0367] The total number of CFU over weeks 1 to 4 was then analyzed by sampling site (interior handle, exterior handle, switch, etc.). A trend toward significance is observed for the treated sites for the exterior door handle (p=0.0765), the switch (p=0.0809) and the adjustable tray (p=0.0809) (Table 8). The lack of power explains the non-significance for the interior handle. For the other elements, the values are much lower in the group of treated rooms, but not in an interpretable manner

TABLE-US-00008 TABLE 8 Total number of CFU per sampling site - Weeks 1 to 4 All rooms Treatment Control (N = 6) (N = 3) (N = 3) p-value CFU Interior handle Weeks 1-4 Mean (SD) 62.33 (36.96) 36.33 (12.1) 88.33 (35.23) 0.1904 Median (Min; Max) 49.5 (27; 117) 32 (27; 50) 99 (49; 117) CFU Exterior handle Weeks 1-4 Mean (SD) 87.33 (30.27) 60.33 (10.12) 114.33 (1.15) 0.0765 Median (Min; Max) 92.5 (54; 115) 55 (54; 72) 115 (113; 115) CFU Switch Weeks 1-4 Mean (SD) 70.17 (31.17) 48 (26.46) 92.33 (15.95) 0.0809 Median (Min; Max) 73.5 (18; 110) 58 (18; 68) 88 (79; 110) CFU Tray Weeks 1-4 Mean (SD) 134 (67.04) 85.67 (30.27) 182.33 (57.55) 0.0809 Median (Min; Max) 126 (58; 246) 81 (58; 118) 167 (134; 246) CFU Toilet Weeks 1-4 Mean (SD) 118 (37.14) 116.33 (11.37) 119.67 (57.54) 1.0000 Median (Min; Max) 117.5 (61; 176) 113 (107; 129) 122 (61; 176) CFU Shower Weeks 1-4 Mean (SD) 251.33 (91.37) 200 (49.76) 302.67 (102.42) 0.3827 Median (Min; Max) 227 (146; 410) 210 (146; 244) 292 (206; 410) CFU Tap Weeks 1-4 Mean (SD) 165.17 (48.35) 138.33 (37.1) 192 (48.03) 0.3827 Median (Min; Max) 158.5 (98; 239) 146 (98; 171) 194 (143; 239)

[0368] The number of colonies of Staphylococcus aureus (MicrococcusBacillus) was studied more particularly.

[0369] Concerning the total colony count, the only trends toward significance (although the count is still much lower in the treated versus untreated rooms) relate to the totality of weeks 1 to 4 (p=0.0765, mean of 424 versus 782 and median of 470 versus 783) and week 3 (p=0.0809, median of 108 for the treated rooms versus 196 for the untreated rooms, or mean of 110 for the treated rooms versus 199 for the untreated rooms) (Table 9).

TABLE-US-00009 TABLE 9 Number of colonies of Staphylococcus aureus (Micrococcus Bacillus) - Weeks 1 to 4 All rooms Treatment Control (N = 6) (N = 3) (N = 3) p-value Total Staph Week 1 Mean (SD) 175.5 (61.59) 142.67 (69.28) 208.33 (38.08) 0.3827 Median (Min; Max) 186.5 (67; 252) 158 (67; 203) 191 (182; 252) Total Staph Week 2 Mean (SD) 156.5 (90.52) 101.33 (57.36) 211.67 (89.8) 0.1904 Median (Min; Max) 156.5 (61; 314) 76 (61; 167) 175 (146; 314) Total Staph Week 3 Mean (SD) 154.67 (55.42) 110 (40.04) 199.33 (9.45) 0.0809 Median (Min; Max) 171.5 (71; 210) 108 (71; 151) 196 (192; 210) Total Staph Week 4 Mean (SD) 116 (71.17) 69.67 (38.37) 162.33 (68.92) 0.1904 Median (Min; Max) 92 (26; 220) 85 (26; 98) 181 (86; 220) Total Staph Weeks 1-4 Mean (SD) 602.67 (203.07) 423.67 (80.25) 781.67 (23.03) 0.0765 Median (Min; Max) 614 (331; 804) 470 (331; 470) 783 (758; 804)

[0370] When the number of colonies of Staphylococcus aureus (MicrococcusBacillus) is compared by sampling site, a trend toward significance is noted for the exterior handle (p=0.0809), the switch (p=0.0809), the adjustable tray (p=0.0809) and the tap (p=0.0809) (Table 10). The values for these locations are substantially lower on the treated sites. For the other locations, the values are always lower on the treated sites but are not significant due to lack of power.

TABLE-US-00010 TABLE 10 Number of colonies of Staphylococcus aureus (Micrococcus Bacillus) by sampling site - Weeks 1 to 4 All rooms Treatment Control (N = 6) (N = 3) (N = 3) p-value Staph Interior handle Weeks 1-4 Mean (SD) 40.17 (26.89) 23.33 (10.97) 57 (28.93) 0.1840 Median (Min; Max) 30 (17; 78) 17 (17; 36) 69 (24; 78) Staph Exterior handle Weeks 1-4 Mean (SD) 64.67 (26.63) 41.67 (8.96) 87.67 (10.26) 0.0809 Median (Min; Max) 65.5 (36; 99) 37 (36; 52) 85 (79; 99) Staph Switch Weeks 1-4 Mean (SD) 43.17 (24.81) 23 (14.73) 63.33 (10.07) 0.0809 Median (Min; Max) 47 (14; 74) 15 (14; 40) 62 (54; 74) Staph Tray Weeks 1-4 Mean (SD) 90.33 (64.67) 37 (17.78) 143.67 (40.07) 0.0809 Median (Min; Max) 85 (23; 189) 31 (23; 57) 129 (113; 189) Staph Toilet Weeks 1-4 Mean (SD) 74.83 (38.04) 57.33 (21.78) 92.33 (47.17) 0.3827 Median (Min; Max) 69.5 (33; 137) 64 (33; 75) 97 (43; 137) Staph Shower Weeks 1-4 Mean (SD) 169 (48.53) 144 (38.74) 194 (50.12) 0.3827 Median (Min; Max) 166 (100; 242) 159 (100; 173) 198 (142; 242) Staph Tap Weeks 1-4 Mean (SD) 120.5 (32.69) 97.33 (10.26) 143.67 (30.92) 0.0809 Median (Min; Max) 112 (86; 178) 100 (86; 106) 135 (118; 178)

[0371] 5.3.2. Weeks 5 to 8

[0372] The same analyses were repeated for weeks 5 to 8.

[0373] The periods of time between cleaning and sampling are all mostly not significant, either week by week or over the last four weeks in total (median of 4.93 hours for the treated rooms versus 4.77 hours for the untreated rooms) (Table 11).

TABLE-US-00011 TABLE 11 Period of time between cleaning and sampling - Weeks 1 to 4 All rooms Treatment Control (N = 6) (N = 3) (N = 3) p-value Time between cleaning and sampling Week 5 Mean (SD) 4.9 (0.46) 5.06 (0.33) 4.74 (0.58) 0.6625 Median (Min; Max) 4.91 (4.38; 5.42) 5.1 (4.71; 5.35) 4.44 (4.38; 5.42) Time between cleaning and sampling Week 6 Mean (SD) 4.71 (0.42) 4.67 (0.06) 4.75 (0.66) 0.6625 Median (Min; Max) 4.71 (4; 5.24) 4.69 (4.6; 4.73) 5 (4; 5.24) Time between cleaning and sampling Week 7 Mean (SD) 5.26 (0.72) 5.15 (0.58) 5.38 (0.95) 1.0000 Median (Min; Max) 4.86 (4.73; 6.48) 4.89 (4.73; 5.81) 4.83 (4.82; 6.48) Time between cleaning and sampling Week 8 Mean (SD) 4.64 (0.49) 4.84 (0.1) 4.44 (0.69) 0.6625 Median (Min; Max) 4.79 (3.65; 4.96) 4.79 (4.77; 4.96) 4.79 (3.65; 4.89) Time between cleaning and sampling Weeks 5-8 Mean (SD) 4.88 (0.41) 4.93 (0.12) 4.83 (0.63) 0.6625 Median (Min; Max) 4.87 (4.23; 5.48) 4.93 (4.81; 5.05) 4.77 (4.23; 5.48)

[0374] For the total number of microorganism colonies, the comparison between groups shows a trend toward significance for week 8, and overall for weeks 5 to 8 taken together (=0.0809). The treated rooms have a median of 571 colonies versus 1056 for the control rooms (Table 12).

TABLE-US-00012 TABLE 12 Total number of CFU - Weeks 5 to 8 All rooms Treatment Control (N = 6) (N = 3) (N = 3) p-value Total CFU Week 5 Mean (SD) 252.33 (151.12) 164.67 (87.23) 340 (162.56) 0.1904 Median (Min; Max) 234 (74; 525) 172 (74; 248) 275 (220; 525) Total CFU Week 6 Mean (SD) 178.33 (59.92) 148.33 (33.95) 208.33 (71.58) 0.1904 Median (Min; Max) 165 (118; 286) 142 (118; 185) 194 (145; 286) Total CFU Week 7 Mean (SD) 221.83 (112.4) 160.33 (68.63) 283.33 (124.62) 0.3827 Median (Min; Max) 199 (83; 366) 184 (83; 214) 344 (140; 366) Total CFU Week 8 Mean (SD) 152.33 (66.79) 94 (16.37) 210.67 (26.03) 0.0809 Median (Min; Max) 146 (76; 236) 98 (76; 108) 212 (184; 236) Total CFU Weeks 5-8 Mean (SD) 804.83 (264.04) 567.33 (60.58) 1042.33 (37.42) 0.0809 Median (Min; Max) 813 (505; 1071) 571 (505; 626) 1056 (1000; 1071)

[0375] By sampling site, a trend toward significance in favor of the treated sites is noted for the interior handle (p=0.0809), the switch (p=0.0809), the toilet lid (p=0.0809) and the shower grab-bar (p=0.0765) (Table 13). In all the cases, the mean and median numbers of microorganism colonies are much lower in the treated sites, the lack of power explaining the non-significance.

TABLE-US-00013 TABLE 13 Total number of CFU per sampling site - Weeks 5 to 8 All rooms Treatment Control (N = 6) (N = 3) (N = 3) p-value CFU Interior handle Weeks 5-8 Mean (SD) 90.33 (50.73) 45 (14) 135.67 (8.5) 0.0809 Median (Min; Max) 94 (35; 144) 39 (35; 61) 136 (127; 144) CFU Exterior handle Weeks 5-8 Mean (SD) 92.83 (27.72) 74.67 (25.7) 111 (16.46) 0.2683 Median (Min; Max) 101.5 (51; 130) 71 (51; 102) 102 (101; 130) CFU Switch Weeks 5-8 Mean (SD) 119 (56.72) 78.67 (32.15) 159.33 (46.14) 0.0809 Median (Min; Max) 114 (42; 212) 92 (42; 102) 140 (126; 212) CFU Tray Weeks 5-8 Mean (SD) 135.83 (59.45) 99.33 (32.81) 172.33 (61.34) 0.1904 Median (Min; Max) 121.5 (77; 227) 84 (77; 137) 184 (106; 227) CFU Toilet Weeks 5-8 Mean (SD) 74 (35.95) 45 (18.08) 103 (19.52) 0.0809 Median (Min; Max) 72.5 (26; 122) 47 (26; 62) 104 (83; 122) CFU Shower Weeks 5-8 Mean (SD) 174.33 (51.11) 128.33 (2.31) 220.33 (13.32) 0.0765 Median (Min; Max) 170 (127; 235) 127 (127; 131) 217 (209; 235) CFU Tap Weeks 5-8 Mean (SD) 126.67 (60.66) 97.33 (10.12) 156 (80.72) 0.6625 Median (Min; Max) 100.5 (66; 222) 92 (91; 109) 180 (66; 222)

[0376] Concerning the number of colonies of Staphylococcus aureus (MicrococcusBacillus), a trend toward significance is noted for week 8 (p=0.0765) and for the totality of weeks 5 to 8 (p=0.0809), with the treated rooms having about half the number of colonies (median of 433 for the treated rooms and 849 for the control rooms) (Table 14).

TABLE-US-00014 TABLE 14 Number of colonies of Staphylococcus aureus (Micrococcus Bacillus) - Weeks 5 to 8 All rooms Treatment Control (N = 6) (N = 3) (N = 3) p-value Total Staph Week 5 Mean (SD) 197.67 (134.32) 127.67 (75.37) 267.67 (157.24) 0.3827 Median (Min; Max) 177 (57; 449) 119 (57; 207) 185 (169; 449) Total Staph Week 6 Mean (SD) 125.83 (51.62) 103 (26.85) 148.67 (66.16) 0.3827 Median (Min; Max) 117.5 (74; 212) 108 (74; 127) 154 (80; 212) Total Staph Week 7 Mean (SD) 188.83 (96.09) 135.33 (65.25) 242.33 (101.19) 0.3827 Median (Min; Max) 171 (64; 310) 150 (64; 192) 291 (126; 310) Total Staph Week 8 Mean (SD) 98.83 (50.6) 54 (5.2) 143.67 (18.56) 0.0765 Median (Min; Max) 91.5 (48; 163) 57 (48; 57) 142 (126; 163) Total Staph Weeks 5-8 Mean (SD) 611.17 (220.42) 420 (66.46) 802.33 (86.08) 0.0809 Median (Min; Max) 591 (348; 855) 433 (348; 479) 849 (703; 855)

[0377] When the number of colonies of Staphylococcus aureus (MicrococcusBacillus) is compared by sampling site, a trend toward significance is noted for the interior handle (p=0.0809), the switch (p=0.0809), the toilet lid (p=0.0809) and the shower grab-bar (p=0.0809) (Table 15). The values for these locations are substantially lower on the treated site. For the other locations, there is also a large decrease in terms of the treated sites versus the untreated sites but the difference does not appear to be significant due to lack of power.

TABLE-US-00015 TABLE 15 Number of colonies of Staphylococcus aureus (Micrococcus Bacillus) by sampling site - Weeks 5 to 8 All rooms Treatment Control (N = 6) (N = 3) (N = 3) p-value Staph Interior handle Weeks 5-8 Mean (SD) 63.83 (41.73) 29 (11.53) 98.67 (24.11) 0.0809 Median (Min; Max) 57 (16; 124) 33 (16; 38) 96 (76; 124) Staph Exterior handle Weeks 5-8 Mean (SD) 67 (25.22) 50.33 (18.23) 83.67 (20.6) 0.1904 Median (Min; Max) 69 (34; 107) 47 (34; 70) 76 (68; 107) Staph Switch Weeks 5-8 Mean (SD) 97.67 (48.63) 68.33 (32.13) 127 (47.95) 0.0809 Median (Min; Max) 93.5 (32; 182) 80 (32; 93) 105 (94; 182) Staph Tray Weeks 5-8 Mean (SD) 103.5 (42.66) 83.67 (37.42) 123.33 (44.38) 0.1904 Median (Min; Max) 100 (55; 160) 70 (55; 126) 136 (74; 160) Staph Toilet Weeks 5-8 Mean (SD) 57.33 (38.89) 29.67 (15.28) 85 (35.37) 0.0809 Median (Min; Max) 44.5 (13; 115) 33 (13; 43) 94 (46; 115) Staph Shower Weeks 5-8 Mean (SD) 127.5 (42.7) 90.33 (18.56) 164.67 (8.39) 0.0809 Median (Min; Max) 131.5 (71; 170) 92 (71; 108) 169 (155; 170) Staph Tap Weeks 5-8 Mean (SD) 94.33 (54.54) 68.67 (16.04) 120 (72.13) 0.6625 Median (Min; Max) 77 (43; 186) 70 (52; 84) 131 (43; 186)

[0378] Lastly, the analysis of the temporal change in the logarithm of the total number of microorganisms in the six rooms involved in the experiment shows a clear trend (p=0.07) toward decrease during the 8 weeks (Table 16, FIG. 1).

TABLE-US-00016 TABLE 16 Mixed model with repeated measures of the natural logarithm of the total number of CFU Effect Estimate Standard error df t value Pr > |t| time 0.04761 0.02569 41 1.85 0.0710

[0379] FIG. 1 shows the change in the logarithm of the total number of CFU over time.

[0380] 5.4. Discussion and Conclusion

[0381] The study by Noyce et al. (Appl Environ Microbiol 2006; 72:4239-4244) is experimental on three strains of Staphylococcus aureus. On copper-coated surfaces, at 22 C., these three strains are killed in 45, 60 and 90 minutes, respectively. On stainless steel-coated surfaces, at 22 C. and after 72 hours, living colonies are found for the three Staphylococcus aureus strains. The authors also find that, at 4 C., the microbial colonies are completely destroyed after 6 hours.

[0382] By using the method of Noyce, Wheeldon et al. (Appl Environ Microbiol 2007; 73:2748-2750; J Antimicrob Chemother 2008; 62:522-525) comparing the effect of a preparation of copper to that of stainless steel on contamination by Clostridium difficile NCTC 11204 and Clostridium difficile 027 R20291. Stainless steel does not show antimicrobial activity against vegetative C. difficile after 30 minutes of exposure (no reduction of activity at 3 hours). On the other hand, copper has antimicrobial activity (p<0.05) against vegetative C. difficile as of 60 minutes after exposure. At 3 hours, with copper, there is a decrease of 99.79% and 99.87% in the logarithm of germinating spores of C. difficile NCTC 11204 and 027 R20291, respectively.

[0383] Casey et al. (J Hosp Infect (2009), doi:10.1016/j.jhin.2009.08.018), by means of a crossover study of the elements of an acute-care ward, compared the number of microorganisms between the elements containing copper and those containing none. After 5 weeks, the elements containing copper and those containing none were interchanged (samples taken once per week at two different hours: 7 a.m. and 5 p.m.). The median values of the number of microorganisms harbored on the copper-containing elements are between 50% and 100% lower than the median values observed in the control group, at 7 a.m. as at 5 p.m. The differences are significant except for one location.

[0384] The 19-room crossover study carried out by Karpanen et al. (Infect. Control Hosp. Epidemiol. 2012; 33:3-9) involved 14 sites in an acute-care ward. The study lasted 24 weeks, with 12 weeks using copper-containing products (more copper 58%) and then 12 weeks without using copper. The number of aerobic microbes and the presence of microorganism indicators were studied. For eight elements out of 14, the authors found significantly fewer microorganisms on the copper-containing products (compared to the products without copper). For the six other elements, the copper-containing products had reduced numbers, but the result was not statistically significant.

[0385] The results that we obtained are in line with those found in the literature, with a lower total number of bacterial colonies for the copper-containing elements. However, we note only a trend toward significance of the decrease in the number of bacteria (this due to a lack of power).

[0386] It is important to note that the ratio of copper present in the proposed alloy is very high (thus comparable to that of other proposed products); the difference is in the thickness of the preparation (200 microns), much thinner than for other products. Consequently, considering the lower cost of this product compared to other copper-containing products, a cost directly related to the total amount of copper (and thus not only to the percentage), and due to the fact that the decrease in the microorganism counts is close to that obtained with larger amounts of copper (similar concentrations), we believe that the proposed product provides a genuine advantage in reducing bacterial carriage and transmission in acute-care wards.

[0387] Lastly, the analysis of the temporal change in the total number of microorganisms within the six rooms leads us to believe that the copper-phosphorized compound used, by decreasing the number of microorganisms in the rooms under study, reduces the contamination of other unprotected rooms.